Altered locus coeruleus–norepinephrine function following single prolonged stress

Sophie A. George · Dayan Knox · Andre L. Curtis · J. Wayne Aldridge · Rita J. Valentino · Israel Liberzon

109 citations0/0 files storedEuropean Journal of Neuroscience

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Posttraumatic Stress Disorder Research Neurotransmitter Receptor Influence on Behavior Stress Responses and Cortisol

Abstract

Data from preclinical and clinical studies have implicated the norepinephrine system in the development and maintenance of post-traumatic stress disorder. The primary source of norepinephrine in the forebrain is the locus coeruleus (LC); however, LC activity cannot be directly measured in humans, and previous research has often relied upon peripheral measures of norepinephrine to infer changes in central LC-norepinephrine function. To directly assess LC-norepinephrine function, we measured single-unit activity of LC neurons in a validated rat model of post-traumatic stress disorder - single prolonged stress (SPS). We also examined tyrosine hydroxylase mRNA levels in the LC of SPS and control rats as an index of norepinephrine utilisation. For electrophysiological recordings, 92 LC neurons were identified from 19 rats (SPS, 12; control, 7), and spontaneous and evoked responses to a noxious event (paw compression) were recorded. Baseline and restraint stress-evoked tyrosine hydroxylase mRNA expression levels were measured in SPS and control rats (n = 16 per group) in a separate experiment. SPS rats showed lower spontaneous activity but higher evoked responses, leading to an enhanced signal-to-noise ratio of LC neurons, accompanied by impaired recovery from post-stimulus inhibition. In concert, tyrosine hydroxylase mRNA expression in the LC of SPS rats tended to be lower at baseline, but was exaggerated following restraint stress. These data demonstrate persistent changes in LC function following stress/trauma in a rat model of post-traumatic stress, as measured by differences in both the electrophysiological properties of LC neurons and tyrosine hydroxylase mRNA transcription.

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References

2013Diagnostic and Statistical Manual of Mental Disorders 2020Diagnostic and Statistical Manual of Mental Disorders 2012Biological studies of post-traumatic stress disorder 1993Abnormal Noradrenergic Function in Posttraumatic Stress Disorder 2006A Parallel Group Placebo Controlled Study of Prazosin for Trauma Nightmares and Sleep Disturbance in Combat Veterans with Post-Traumatic Stress Disorder 1987Sustained urinary norepinephrine and epinephrine elevation in post-traumatic stress disorder 2009Single prolonged stress: toward an animal model of posttraumatic stress disorder 1999Neuroendocrine and Psychophysiologic Responses in PTSD: A Symptom Provocation Study

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2017Post-Traumatic Stress Disorder: The Relationship Between the Fear Response and Chronic Stress 2016Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress 2019The effects of trauma on brain and body: A unifying role for the midbrain periaqueductal gray

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